Protease-Responsive Hydrogel Microparticles for Intradermal Drug Delivery
(2023) In Biomacromolecules 24(7). p.3203-3214- Abstract
Protease-responsive multi-arm polyethylene glycol-based microparticles with biscysteine peptide crosslinkers (CGPGG↓LAGGC) were obtained for intradermal drug delivery through inverse suspension photopolymerization. The average size of the spherical hydrated microparticles was ∼40 μm after crosslinking, making them attractive as a skin depot and suitable for intradermal injections, as they are readily dispensable through 27G needles. The effects of exposure to matrix metalloproteinase 9 (MMP-9) on the microparticles were evaluated by scanning electron microscopy and atomic force microscopy, demonstrating partial network destruction and decrease in elastic moduli. Given the recurring course of many skin diseases, the microparticles were... (More)
Protease-responsive multi-arm polyethylene glycol-based microparticles with biscysteine peptide crosslinkers (CGPGG↓LAGGC) were obtained for intradermal drug delivery through inverse suspension photopolymerization. The average size of the spherical hydrated microparticles was ∼40 μm after crosslinking, making them attractive as a skin depot and suitable for intradermal injections, as they are readily dispensable through 27G needles. The effects of exposure to matrix metalloproteinase 9 (MMP-9) on the microparticles were evaluated by scanning electron microscopy and atomic force microscopy, demonstrating partial network destruction and decrease in elastic moduli. Given the recurring course of many skin diseases, the microparticles were exposed to MMP-9 in a flare-up mimicking fashion (multiple-time exposure), showing a significant increase in release of tofacitinib citrate (TC) from the MMP-responsive microparticles, which was not seen for the non-responsive microparticles (polyethylene glycol dithiol crosslinker). It was found that the degree of multi-arm complexity of the polyethylene glycol building blocks can be utilized to tune not only the release profile of TC but also the elastic moduli of the hydrogel microparticles, with Young’s moduli ranging from 14 to 140 kPa going from 4-arm to 8-arm MMP-responsive microparticles. Finally, cytotoxicity studies conducted with skin fibroblasts showed no reduction in metabolic activity after 24 h exposure to the microparticles. Overall, these findings demonstrate that protease-responsive microparticles exhibit the properties of interest for intradermal drug delivery.
(Less)
- author
- Noddeland, Heidi K. ; Lind, Marianne ; Petersson, Karsten ; Caruso, Frank ; Malmsten, Martin LU and Heinz, Andrea
- organization
- publishing date
- 2023-07-10
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Biomacromolecules
- volume
- 24
- issue
- 7
- pages
- 12 pages
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- pmid:37307231
- scopus:85164252126
- ISSN
- 1525-7797
- DOI
- 10.1021/acs.biomac.3c00265
- language
- English
- LU publication?
- yes
- id
- 8fe1955a-54f3-4189-9afd-664da37bcaf7
- date added to LUP
- 2023-10-06 14:09:18
- date last changed
- 2024-04-19 02:02:02
@article{8fe1955a-54f3-4189-9afd-664da37bcaf7,
abstract = {{<p>Protease-responsive multi-arm polyethylene glycol-based microparticles with biscysteine peptide crosslinkers (CGPGG↓LAGGC) were obtained for intradermal drug delivery through inverse suspension photopolymerization. The average size of the spherical hydrated microparticles was ∼40 μm after crosslinking, making them attractive as a skin depot and suitable for intradermal injections, as they are readily dispensable through 27G needles. The effects of exposure to matrix metalloproteinase 9 (MMP-9) on the microparticles were evaluated by scanning electron microscopy and atomic force microscopy, demonstrating partial network destruction and decrease in elastic moduli. Given the recurring course of many skin diseases, the microparticles were exposed to MMP-9 in a flare-up mimicking fashion (multiple-time exposure), showing a significant increase in release of tofacitinib citrate (TC) from the MMP-responsive microparticles, which was not seen for the non-responsive microparticles (polyethylene glycol dithiol crosslinker). It was found that the degree of multi-arm complexity of the polyethylene glycol building blocks can be utilized to tune not only the release profile of TC but also the elastic moduli of the hydrogel microparticles, with Young’s moduli ranging from 14 to 140 kPa going from 4-arm to 8-arm MMP-responsive microparticles. Finally, cytotoxicity studies conducted with skin fibroblasts showed no reduction in metabolic activity after 24 h exposure to the microparticles. Overall, these findings demonstrate that protease-responsive microparticles exhibit the properties of interest for intradermal drug delivery.</p>}},
author = {{Noddeland, Heidi K. and Lind, Marianne and Petersson, Karsten and Caruso, Frank and Malmsten, Martin and Heinz, Andrea}},
issn = {{1525-7797}},
language = {{eng}},
month = {{07}},
number = {{7}},
pages = {{3203--3214}},
publisher = {{The American Chemical Society (ACS)}},
series = {{Biomacromolecules}},
title = {{Protease-Responsive Hydrogel Microparticles for Intradermal Drug Delivery}},
url = {{http://dx.doi.org/10.1021/acs.biomac.3c00265}},
doi = {{10.1021/acs.biomac.3c00265}},
volume = {{24}},
year = {{2023}},
}